Cell Proliferation最新文献

{"title":"Lin28a forms an RNA-binding complex with Igf2bp3 to regulate m⁶A-modified stress response genes in stress granules of muscle stem cells.","authors":"Dan Song, Yu Chen, Peng Wang, Yeqian Cheng, Ng Shyh-Chang","doi":"10.1111/cpr.13707","DOIUrl":"https://doi.org/10.1111/cpr.13707","url":null,"abstract":"<p><p>In the early embryonic stages, Lin-28 homologue A (Lin28a) is highly expressed and declines as the embryo matures. As an RNA-binding protein, Lin28a maintains some adult muscle stem cells (MuSCs) in an embryonic-like state, but its RNA metabolism regulation mechanism remains unclear. BioGPS analysis revealed that Lin28a expression is significantly higher in muscle tissues than in other tissues. Lin28a-positive muscle stem cells (Lin28a+ MuSCs) were sorted from Lin28a-CreERT2; LSL-tdTomato mouse skeletal muscle tissue, which exhibited a higher proliferation rate than the control group. Lin28a-bound transcripts are enriched in various biological processes such as DNA repair, cell cycle, mitochondrial tricarboxylic acid cycle and oxidative stress response. The expression of insulin-like growth factor 2 mRNA-binding protein 3 (Igf2bp3) was markedly elevated in the presence of Lin28a. Co-immunoprecipitation analysis further demonstrated that Lin28a associates with Igf2bp3. Immunofluorescence analyses confirmed that Lin28a, Igf2bp3 and G3bp1 colocalize to form stress granules (SG), and N6-methyladenosine (m⁶A) modification promotes the formation of Lin28a-SG. Sequencing of the transcriptome and RNAs immunoprecipitated by Lin28a, Igf2bp3 and m⁶A antibodies in Lin28a+ MuSCs further revealed that Lin28a and Igf2bp3 collaboratively regulate the expression of DNA repair-related genes, including Fancm and Usp1. Lin28a stabilises Igf2bp3, Usp1, and Fancm mRNAs, enhancing DNA repair against oxidative or proteotoxic stress, thus promoting MuSCs self-renewal. Understanding the intricate mechanisms through which Lin28a and Igf2bp3 regulate MuSCs provides a deeper understanding of stem cell self-renewal, with potential implications for regenerative medicine.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13707"},"PeriodicalIF":5.9,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compromised cell competition exhausts neural stem cells pool.","authors":"Chenxiao Li, Mengtian Zhang, Yushan Du, Shuang Liu, Da Li, Shukui Zhang, Fen Ji, Jingjing Zhang, Jianwei Jiao","doi":"10.1111/cpr.13710","DOIUrl":"https://doi.org/10.1111/cpr.13710","url":null,"abstract":"<p><p>Blood vessels play a crucial role in maintaining the stem cell niche in both tumours and developing organs. Cell competition is critical for tumour progression. We hypothesise that blood vessels may act as a regulator of this process. As a pioneer, the secretions of blood vessels regulate the intensity of cell competition, which is essential for tumour invasion and developmental organ extension. Brd4 expresses highly in endothelial cells within various tumours and is positively correlated with numerous invasive genes, making it an ideal focal point for further research on the relationship between blood vessels and cell competition. Our results indicated that the absence of endothelial Brd4 led to a reduction in neural stem cell mortality and compromised cell competition. Endothelial Brd4 regulated cell competition was dependent on Testican2. Testican2 was capable of depositing Sparc and acted as a suppressor of Sparc. Compromised cell competition resulted in the depletion of neural stem cells and accelerated brain ageing. Testican2 could rescue the run-off of neural stem cells and accelerate the turnover rate of neurons. AD patients show compromised cell competition. Through the cloning of a point mutant of Brd4 identified in a subset of AD patients, it was demonstrated that the mutant lacked the ability to promote cell competition. This study suggests a novel approach for treating age-related diseases by enhancing the intensity of cell competition.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13710"},"PeriodicalIF":5.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired autophagy-mediated macrophage polarization contributes to age-related hyposalivation.","authors":"Zhili Xin, Rongyao Xu, Yangjiele Dong, Shenghao Jin, Xiao Ge, Xin Shen, Songsong Guo, Yu Fu, Ping Zhang, Hongbing Jiang","doi":"10.1111/cpr.13714","DOIUrl":"https://doi.org/10.1111/cpr.13714","url":null,"abstract":"<p><p>Age-related dysfunction of salivary glands (SGs) leading to xerostomia or dry mouth is typically associated with increased dental caries and difficulties in mastication, deglutition or speech. Inflammaging-induced hyposalivation plays a significant role in aged SGs; however, the mechanisms by which ageing shapes the inflammatory microenvironment of SGs remain unclear. Here, we show that reduced salivary secretion flow rate in aged human and mice SGs is associated with impaired autophagy and increased M1 polarization of macrophages. Our study reveals the crucial roles of SIRT6 in regulating macrophage autophagy and polarization through the PI3K/AKT/mTOR pathway, as demonstrated by generating two conditional knock out mice. Furthermore, triptolide (TP) effectively rejuvenates macrophage autophagy and polarization via targeting this pathway. We also design a local delivery of TP-loaded apoptotic extracellular vesicles (ApoEVs) to improve age-related SGs dysfunction therapeutically. Collectively, our findings uncover a previously unknown link between SIRT6-regulated autophagy and macrophage polarization in age-mediated hyposalivation, while our locally therapeutic strategy exhibits potential preventive effects for age-related hyposalivation.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13714"},"PeriodicalIF":5.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory inflation: Beyond the acute phase of viral infection.","authors":"Yanfei Li, Jie Xiao, Chen Li, Mu Yang","doi":"10.1111/cpr.13705","DOIUrl":"https://doi.org/10.1111/cpr.13705","url":null,"abstract":"<p><p>Memory inflation is confirmed as the most commonly dysregulation of host immunity with antigen-independent manner in mammals after viral infection. By generating large numbers of effector/memory and terminal differentiated effector memory CD8⁺ T cells with diminished naïve subsets, memory inflation is believed to play critical roles in connecting the viral infection and the onset of multiple diseases. Here, we reviewed the current understanding of memory inflated CD8⁺ T cells in their distinct phenotypic features that different from exhausted subsets; the intrinsic and extrinsic roles in regulating the formation of memory inflation; and the key proteins in maintaining the expansion and proliferation of inflationary populations. More importantly, based on the evidences from both clinic and animal models, we summarized the potential mechanisms of memory inflation to trigger autoimmune neuropathies, such as Guillain-Barré syndrome and multiple sclerosis; the correlations of memory inflation between tumorigenesis and resistance of tumour immunotherapies; as well as the effects of memory inflation to facilitate vascular disease progression. To sum up, better understanding of memory inflation could provide us an opportunity to beyond the acute phase of viral infection, and shed a light on the long-term influences of CD8⁺ T cell heterogeneity in dampen host immune homeostasis.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13705"},"PeriodicalIF":5.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabaging cycle promotes non-metabolic chronic diseases of ageing","authors":"Yeqian Cheng,&nbsp;Ruirui Liu,&nbsp;Ruiqi Rachel Wang,&nbsp;Kang Yu,&nbsp;Ji Shen,&nbsp;Jing Pang,&nbsp;Tiemei Zhang,&nbsp;Hong Shi,&nbsp;Liang Sun,&nbsp;Ng Shyh-Chang","doi":"10.1111/cpr.13712","DOIUrl":"10.1111/cpr.13712","url":null,"abstract":"&lt;p&gt;The global trend of population ageing is intertwined with the rising incidence of metabolic diseases such as obesity and muscle atrophy, posing a formidable challenge to human health. A more profound understanding of the mechanisms linking metabolic and chronic diseases can enhance the standard of human health and contribute to achieving healthy ageing.&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; The Metabaging Cycle concept introduced by Ma and Shyh-Chang in 2022&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; unveiled the intricate interplay between metabolic dysregulation and inflammation in both adipose and muscle tissue, ultimately leading to the occurrence of obesity and muscle atrophy. Specifically, excesive lipids not only promote inflammation and ageing processes in adipose tissue, diminishing the secretion of beneficial adipose factors, but also triggers muscle fat infiltration and mitochondrial dysfunction. The interaction between inflammatory factors and adipose or muscle tissue further exacerbates systemic insulin resistance and chronic inflammation.&lt;/p&gt;&lt;p&gt;The Metabaging Cycle theory underscores the close connection between metabolic health in muscle and adipose tissue and overall well-being, which manifests especially clearly in pathological conditions like obesity, insulin resistance and cachexia. This vicious cycle serves as a driving force for various chronic metabolic syndrome diseases and further promotes the pathogenesis of non-metabolic chronic diseases of ageing such as neurodegenerative diseases, osteoporosis, arthritis and cancer (Figure 1).&lt;span&gt;&lt;sup&gt;6-10&lt;/sup&gt;&lt;/span&gt; Hence, from the perspective of the Metabaging Cycle theory, disrupting this malignant cycle stands as a key strategy in preventing and treating a large variety of chronic diseases of ageing, holding significant importance in reducing the incidence risk of chronic diseases and enhancing overall health.&lt;/p&gt;&lt;p&gt;In the field of neuroscience, chronic inflammatory states have been confirmed as a critical pathogenic factor.&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; This inflammatory state, through sustained stimulation by inflammatory mediators such as cytokines and free radicals, triggers neuronal damage and neurodegenerative changes. Specifically, cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) play essential roles in the process of neuroinflammation, activating microglial cells and astrocytes to produce more inflammatory mediators, creating a vicious cycle and positive feedback loop that exacerbates neuronal damage.&lt;span&gt;&lt;sup&gt;12-14&lt;/sup&gt;&lt;/span&gt; Furthermore, free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) can directly damage neuronal membranes, leading to lipid peroxidation and protein oxidation, disrupting the normal function and structure of neurons.&lt;span&gt;&lt;sup&gt;15&lt;/sup&gt;&lt;/span&gt; This inflammation disrupts neuronal function and structure and interferes with nerve cell metabolism and signal transduction, accelerating the development of neurod","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell sequencing reveals the transcriptional alternations of 17β-estradiol suppressing primordial follicle formation in neonatal mouse ovaries","authors":"Yutong Yan,&nbsp;Hui Zhang,&nbsp;Rui Xu,&nbsp;Linglin Luo,&nbsp;Lu Yin,&nbsp;Hao Wu,&nbsp;Yiqian Zhang,&nbsp;Chan Li,&nbsp;Sihai Lu,&nbsp;Yaju Tang,&nbsp;Xiaoe Zhao,&nbsp;Menghao Pan,&nbsp;Qiang Wei,&nbsp;Sha Peng,&nbsp;Baohua Ma","doi":"10.1111/cpr.13713","DOIUrl":"10.1111/cpr.13713","url":null,"abstract":"<p>Estrogen has been implicated in multiple biological processes, but the variation underlying estrogen-mediated primordial follicle (PF) formation remains unclear. Here, we show that 17β-estradiol (E₂) treatment of neonatal mice led to the inhibition of PF formation and cell proliferation. Single-cell RNA sequencing (scRNA-seq) revealed that E₂ treatment caused significant changes in the transcriptome of oocytes and somatic cells. E₂ treatment disrupted the synchronised development of oocytes, pre-granulosa (PG) cells and stromal cells. Mechanistically, E₂ treatment disrupted several signalling pathways critical to PF formation, especially down-regulating the Kitl and Smad1/3/4/5/7 expression, reducing the frequency and number of cell communication. In addition, E₂ treatment influenced key gene expression, mitochondrial function of oocytes, the recruitment and maintenance of PG cells, the cell proliferation of somatic cells, as well as disordered the ovarian microenvironment. This study not only revealed insights into the regulatory role of estrogen during PF formation, but also filled in knowledge of dramatic changes in perinatal hormones, which are critical for the physiological significance of understanding hormone changes and reproductive protection.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A regulatory loop of JAK/STAT signalling and its downstream targets represses cell fate conversion and maintains male germline stem cell niche homeostasis","authors":"Ruiyan Kong,&nbsp;Hang Zhao,&nbsp;Juan Li,&nbsp;Yankun Ma,&nbsp;Ningfang Li,&nbsp;Lin Shi,&nbsp;Zhouhua Li","doi":"10.1111/cpr.13648","DOIUrl":"10.1111/cpr.13648","url":null,"abstract":"<p>A specialised microenvironment, termed niche, provides extrinsic signals for the maintenance of residential stem cells. However, how residential stem cells maintain niche homeostasis and whether stromal niche cells could convert their fate into stem cells to replenish lost stem cells upon systemic stem cell loss remain largely unknown. Here, through systemic identification of JAK/STAT downstream targets in adult <i>Drosophila</i> testis, we show that Escargot (Esg), a member of the Snail family of transcriptional factors, is a putative JAK/STAT downstream target. <i>esg</i> is intrinsically required in cyst stem cells (CySCs) but not in germline stem cells (GSCs). <i>esg</i> depletion in CySCs results in CySC loss due to differentiation and non-cell autonomous GSC loss. Interestingly, hub cells are gradually lost by delaminating from the hub and converting into CySCs in <i>esg</i>-<i>defective</i> testes. Mechanistically, <i>esg</i> directly represses the expression of <i>socs36E</i>, the well-known downstream target and negative regulator of JAK/STAT signalling. Finally, further depletion of <i>socs36E</i> completely rescues the defects observed in <i>esg</i>-<i>defective</i> testes. Collectively, JAK/STAT target Esg suppresses SOCS36E to maintain CySC fate and repress niche cell conversion. Thus, our work uncovers a regulatory loop between JAK/STAT signalling and its downstream targets in controlling testicular niche homeostasis under physiological conditions.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneous stiffness of the bone marrow microenvironment regulates the fate decision of haematopoietic stem and progenitor cells.","authors":"Guolin Shi, Zhuo Chang, Pan Zhang, Xiaohang Zou, Xinmin Zheng, Xiru Liu, Jinxiao Yan, Huiyun Xu, Zhenhao Tian, Nu Zhang, Ning Cui, Leming Sun, Guangkui Xu, Hui Yang","doi":"10.1111/cpr.13715","DOIUrl":"https://doi.org/10.1111/cpr.13715","url":null,"abstract":"<p><p>The bone marrow (BM) niches are the complex microenvironments that surround cells, providing various external stimuli to regulate a range of haematopoietic stem cell (HSC) behaviours. Recently, it has been proposed that the fate decision of HSCs is often correlated with significantly altered biophysical signals of BM niches. To thoroughly elucidate the effect of mechanical microenvironments on cell fates, we constructed 2D and 3D cell culture hydrogels using polyacrylamide to replicate the mechanical properties of heterogeneous sub-niches, including the inherent rigidity of marrow adipose tissue (2 kPa), perivascular tissue (8 kPa) and endosteum region (35 kPa) in BM. Our observations suggest that HSCs can respond to the mechanical heterogeneity of the BM microenvironment, exhibiting diversity in cell mechanics, haematopoietic pool maintenance and differentiated lineages. Hydrogels with higher stiffness promote the preservation of long-term repopulating HSCs (LT-HSCs), while those with lower stiffness support multi-potent progenitors (MPPs) viability in vitro. Furthermore, we established a comprehensive transcriptional profile of haematopoietic subpopulations to reflect the multipotency of haematopoietic stem and progenitor cells (HSPCs) that are modulated by niche-like stiffness. Our findings demonstrate that HSPCs exhibit completely distinct downstream differentiated preferences within hydrogel systems of varying stiffness. This highlights the crucial role of tissue-specific mechanical properties in HSC lineage decisions, which may provide innovative solutions to clinical challenges.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13715"},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Octyl itaconate blocks GSDMB-mediated pyroptosis and restricts inflammation by inactivating granzyme A.","authors":"Wenbin Gong, Hangyu Fu, Kui Yang, Tao Zheng, Kun Guo, Wei Zhao","doi":"10.1111/cpr.13711","DOIUrl":"https://doi.org/10.1111/cpr.13711","url":null,"abstract":"<p><p>GSDMB-mediated pyroptosis facilitates a pro-inflammatory immune microenvironment and needs to be tightly regulated to avoid excessive inflammation. Here, we provide evidence that itaconate and its cell-permeable derivative 4-octyl itaconate (4-OI) can significantly inhibit GSDMB-rendered pyroptotic activity independent of Nrf2. 4-OI interferes proteolytic process of GSDMB by directly modifying Cys54, Cys148 and Ser212 on granzyme A (GrzA), a serine protease that site-specifically cleaves the inter-domain linker of GSDMB, instead of interaction with GSDMB, thereby blocking pyroptosis and exerts anti-inflammatory effects. Moreover, 4-OI alleviates inflammation by suppressing GSDMB-induced pyroptotic cell death during acute colitis models in intestinal epithelial GSDMB conditional transgenic mice. Our data expand the role of 4-OI as a crucial immunometabolic derivative that regulates innate immunity and inflammation through a newly identified posttranslational modification, and targeting of pyroptosis by 4-OI therefore holds potent therapeutic potential for primarily inflammatory and/or autoimmune diseases.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13711"},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of CD151 overexpression on prognosis and therapy in non-small cell lung cancer patients lacking EGFR mutations","authors":"Amanda Huee-Ping Wong,&nbsp;Min En Nga,&nbsp;Chin Yein Chin,&nbsp;Yee Kit Tai,&nbsp;Hung Chew Wong,&nbsp;Ross Soo,&nbsp;Omer An,&nbsp;Henry Yang,&nbsp;Ju Ee Seet,&nbsp;Yaw Chyn Lim,&nbsp;John Kit Chung Tam,&nbsp;Thai Tran","doi":"10.1111/cpr.13708","DOIUrl":"10.1111/cpr.13708","url":null,"abstract":"<p>This study investigates CD151, a protein linked to cancer progression, in non-small cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations. These patients often have limited treatment options. The study used retrospective analysis to examine 157 adenocarcinoma biopsy specimens and 199 patient cases from The Cancer Genome Atlas, correlating CD151 expression with patient survival. Cellular studies revealed that CD151 interacts with EGFR, influencing epidermal growth factor (EGF)-induced cell proliferation and the effectiveness of the EGFR inhibitor, erlotinib. A strong association was found between CD151 expression and EGFR mutation status. High CD151 expression in the absence of EGFR mutations is correlated with poorer survival outcomes. Biological assays showed that CD151 colocalizes and associates with EGFR, playing a crucial role in regulating EGF-induced cell proliferation via the AKT and ERK1/2 pathways. Importantly, CD151 expression was found to influence the anti-proliferative effects of the EGFR tyrosine kinase inhibitor, erlotinib. High CD151 expression, in the absence of EGFR mutations, was associated with poorer survival outcomes. It could serve as a potential prognostic marker and influence cellular responses to EGFR-targeted treatments. This study highlights CD151 as a potential novel target for therapeutic intervention in NSCLC, especially in populations lacking EGFR mutations.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}